PH Domain And Leucine Rich Repeat Protein Phosphatase 2 (PHLPP2)

The deduced 1,323-amino acid PHLPP2 protein contains an N-terminal pleckstrin homology (PH) domain, followed by leucine-rich repeats, a phosphatase domain, and a C-terminal PDZ-binding domain. PHLPP2 shares 50% amino acid identity with PHLPP. Immunohistochemical analysis detected PHLPP2 expression throughout normal breast cells, and cell fractionation revealed PHLPP2 in cytosolic, membrane, and nuclear fractions.

PHLPP2 did not significantly dephosphorylate other kinases examined. Immunoprecipitation analysis of human embryonic kidney cells showed that endogenous AKT bound PHLPP2. Following EGF stimulation, both PHLLP1 and PHLPP2 limited the amplitude of agonist-dependent phosphorylation of AKT on both thr308 and ser473.